caa a22 4500 569207703 20200912030139.0 cr unu---uuuuu 190724e201711 xx s 000 0 eng (BORIS)oai:boris.unibe.ch:122918 610 ddc Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling [Elektronische Daten] [Heinz-Dieter Müller, Jordi Caballé Serrano, Adrian Lussi, Reinhard Gruber] publishedVersion openAccess eu-repo OBJECTIVES Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires toll-like receptor 4 signaling. MATERIAL AND METHODS To test this hypothesis, we blocked toll-like receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures. Osteoclastogenesis was evaluated based on gene expression analysis and histochemical staining for tartrate-resistant acid phosphatase. Resorption was performed on dentine. RESULTS We report that TAK-242 reversed the inhibitory effect of fresh sterile saliva on the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase. In line with this finding, TAK-242 increased the expression of the osteoclast functional genes cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase in the presence of saliva. TAK-242 also supported the expression of NFATc1, the master regulator of osteoclastogenesis, as well as DC-STAMP and Atp6v0d2, both being cell fusion genes. In support of the hypothesis, depletion of saliva from endotoxin partially reversed the inhibitory effect on osteoclastogenesis. Moreover, salivary pellicle on plastic and titanium did not affect osteoclastogenesis. CONCLUSION Inhibition of toll-like receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts. CLINICAL RELEVANCE Saliva can activate pattern recognition receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts. Müller Heinz-Dieter joint author Caballé Serrano Jordi joint author Lussi Adrian joint author Gruber Reinhard joint author Clinical oral investigations 21(8), pp. 2445-2452 Onlinezugriff via WWW text/html Müller, Heinz-Dieter; Caballé Serrano, Jordi; Lussi, Adrian; Gruber, Reinhard (2017). Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling. Clinical oral investigations, 21(8), pp. 2445-2452. Springer-Verlag 10.1007/s00784-016-2041-7 <http://dx.doi.org/10.1007/s00784-016-2041-7> BORIS BK010053 XK010053 XK010000 1 info:eu-repo/semantics/article boris PeerReviewed boris peerstatus BORIS BORIS BORIS info:eu-repo/semantics/article openAccess BORIS 856 42 Onlinezugriff via WWW text/html Müller, Heinz-Dieter; Caballé Serrano, Jordi; Lussi, Adrian; Gruber, Reinhard (2017). Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling. Clinical oral investigations, 21(8), pp. 2445-2452. Springer-Verlag 10.1007/s00784-016-2041-7 <http://dx.doi.org/10.1007/s00784-016-2041-7> BORIS 700 1- Müller Heinz-Dieter joint author BORIS 700 1- Caballé Serrano Jordi joint author BORIS 700 1- Lussi Adrian joint author BORIS 700 1- Gruber Reinhard joint author BORIS 773 0- Clinical oral investigations 21(8), pp. 2445-2452